Como Protocolos Inovadores são Criados e Adotados em Escala Mundial: Uma visão sobre o Internet Engineering Task Force (IETF) e a Infraestrutura da Internet

The IETF is responsible for the standardization and development of Internet protocols and this is based on the voluntary participation ofprofessionals, academics, and resear- chers from around the world. Volunteers work together through email lists and in three face-to-face meetings yearly. This proposal considers the importance ofidentifying mul- tidisciplinary opportunities around the Internet Engineering Task Force (IETF) in the process ofcreating or improving innovative standards on the Internet. We will discuss the organization of working groups, highlighting discussions ranging from protocols known as the Internet Protocol (IP) to research groups such as Things-to-Things (T2TRG) that discuss standards on the Internet ofThings (IoT). The opportunity to discuss theoretical/- practical challenges and manners of collaboration at the IETF opens up a vast prospect ofinclusion for the Brazilian community, as it becomes aware ofhow the IETF is consti- tuted and remains active, vigilant and prepared for the necessary changes for the smooth functioning of the Internet. The multidisciplinary, in the field of computing science that aggregates the volunteering of the IETF, is evident and needs the active help of people with diversified knowledge and in areas other than, necessarily, networks. In this way, this chapter covers since basic foundations on the Internet, the functioning of the IETF, the process ofdevelopment ofnew protocols, as well as the necessary tools and rules for writing an Internet-Draft (I-D).

The Genetic Polymorphism of TNF-α Associated with the Anti-TNF-α Therapy Used for COVID-19 Patients – Another Possible Approach

Objective: This work aimed of to review the implications of anti-TNF-α therapy in COVID-19 patients associated with the genetic polymorphism (TNF-α polymorphisms in the region-308) of this pertinent cytokine Methodology: Electronic searches were carried out on PUBMED Central, BVS/BIREME, Web of Science and The Cochrane Library with the aid of key-words. Results: Twenty-six articles were collected. Anti-TNF-α therapy was interpreted and evaluated. Conclusions: Although scarce information is available in the current literature, anti- TNF-α therapy seems to be a viable clinical approach for hospitalized COVID-19 patients who do not need oxygen supply. The genetic polymorphisms, although relevant, may be useful for further researched to assess the clinical response in different research groups.

Short-Term Storability of Alginate-Encapsulated Persian Violet Microshoots for Germplasm Exchange

Microshoots have been widely used for micropropagation. It may be necessary to store microshoots for a short period of time, for example in germplasm exchange needing transport to other research groups. Here, we investigated the short-term storability of alginate-encapsulated Persian violet (Exacum affine Balf. f. ex Regel) microshoots at 4 °C and 25 °C. After storage, the encapsulated microshoots were sown on basal Murashige and Skoog medium for germination and viability determination using tetrazolium chloride staining. The results showed that one or five microshoots encapsulated with a single alginate layer could be stored at 4 °C for up to 30 days, while the percentages of germination and viability of the microshoots encapsulated with two layers of alginate were greatly reduced upon storage. This is the first report on the storability of alginate-encapsulated multiple microshoots, which could be a more efficient way to encapsulate microshoots used for short-term cold storage.

Clinical Significance and Regulation of ERK5 Expression and Function in Cancer

Extracellular signal-regulated kinase 5 (ERK5) is a unique kinase among MAPKs family members, given its large structure characterized by the presence of a unique C-terminal domain. Despite increasing data demonstrating the relevance of the ERK5 pathway in the growth, survival, and differentiation of normal cells, ERK5 has recently attracted the attention of several research groups given its relevance in inflammatory disorders and cancer. Accumulating evidence reported its role in tumor initiation and progression. In this review, we explore the gene expression profile of ERK5 among cancers correlated with its clinical impact, as well as the prognostic value of ERK5 and pERK5 expression levels in tumors. We also summarize the importance of ERK5 in the maintenance of a cancer stem-like phenotype and explore the major known contributions of ERK5 in the tumor-associated microenvironment. Moreover, although several questions are still open concerning ERK5 molecular regulation, different ERK5 isoforms derived from the alternative splicing process are also described, highlighting the potential clinical relevance of targeting ERK5 pathways.

Do Human iPSC-Derived Cardiomyocytes Cultured on PLA Scaffolds Induce Expression of CD28/CTLA-4 by T Lymphocytes?

Many research groups have developed various types of tissue-engineered cardiac constructs. However, the immunological properties of such artificial tissues are not yet fully understood. Previously, we developed microfiber scaffolds carrying human iPSC-derived cardiomyocytes (hiPSC-CM). In this work, we evaluated the ability of these tissue-engineered constructs to activate the expression of CD28 and CTLA-4 proteins on T lymphocytes, which are early markers of the immune response. For this purpose, electrospun PLA microfiber scaffolds were seeded with hiPSC-CM and cultured for 2 weeks. Allogeneic mononuclear cells were then co-cultured for 48 h with three groups of samples: bare scaffolds, pure cardiomyocyte culture and tissue-engineered constructs, followed by analysis of CD28/CTLA-4 expression on T lymphocytes using flow cytometry. PLA scaffolds and concanavalin A stimulation (positive control) statistically significantly increased CD28 expression on CD4+ T cells (up to 61.3% and 66.3%) CD8+ T cells (up to 17.8% and 21.7%). CD28/CTLA-4 expression was not increased when T lymphocytes were co-cultured with cardiac tissue-engineered constructs and iPSC-CM monolayers. Thus, iPSC-CM in monolayers and on PLA microfiber scaffolds did not induce T cell activation, which suggests that such cardiac constructs would not be a cause of rejection after implantation.

Metal-as-Insulation HTS coils

In this article, we summarize what we have learned about Metal-as-Insulation (MI) winding behavior and technical challenges. Bailey et al. first proposed the use of Metallic Insulation (MI) for superconducting magnet in 1988 through a U.S. patent. High Temperature Superconductor (HTS) materials are highly thermally stable. This feature compared to classical Low Temperature Superconductor (LTS) enables the use of MI technology to improve the protection against quenches. Gupta was the first to propose the use of a metallic tape in an HTS winding to avoid too much radial currents in No Insulation (NI) in 2011. Hahn et al. presented preliminary results on a pancake sample the same year. We are proposing here to come back on the work done for about 10 years by research groups worldwide and will focus on the turn-to-turn contact resistivity Rct parameter. We will also give details of our LNCMI-CEA-Néel Institute MI HTS insert built in 2018 in the framework of the French National Research Agency (ANR) funding through the NOUGAT project. We tested this magnet many times between 2018 and 2021 and learnt a lot on this technology. This magnet is the first REBCO solenoid of this size using this technology and tested intensively at such high magnetic field (up to 32.5 T) so far. In this magnet, we firstly include a magnetic shielding technology consisting of REBCO NI turns inside the overbanding of each pancake. We give some details and effect of such technology inside an HTS MI insert in case of a fast discharge, a quench or an outsert failure. Finally, we discuss about the self-protection feature of MI coils and we propose a passive protection way for high Rct values.

Resilient Clinical Trial Infrastructure in Response to the COVID-19 Pandemic: Lessons Learned from the TOGETHER Randomized Platform Clinical Trial

In response to the COVID-19 pandemic, clinical research groups across the world developed trial protocols to evaluate the safety and efficacy of treatments for COVID-19. Despite this initial enthusiasm, only a small portion of these protocols were implemented. Of those implemented, a fraction successfully recruited their target sample size to analyze and disseminate findings. More than a year and a half into the COVID-19 pandemic, only a few clinical trials evaluating treatments for COVID-19 have generated new evidence. Productive randomized platform clinical trials evaluating COVID-19 treatments may attribute their success to intentional investments in developing resilient clinical trial infrastructures. Health system resiliency discourse provides a conceptual framework for characterizing attributes for withstanding shocks. This framework may also be useful for contextualizing the attributes of productive clinical trials evaluating COVID-19 therapies. We characterize the successful attributes and lessons learned in developing the TOGETHER Trial infrastructure using a health system resiliency framework. This framework may be considered by clinical trialists aiming to build resilient trial infrastructures capable of responding rapidly and efficiently to global health threats.

STRIDE: a command-line HMM-based identifier and sub-classifier of Plasmodium falciparum RIFIN and STEVOR variant surface antigen families

Background RIFINs and STEVORs are variant surface antigens expressed by P. falciparum that play roles in severe malaria pathogenesis and immune evasion. These two highly diverse multigene families feature multiple paralogs, making their classification challenging using traditional bioinformatic methods. Results STRIDE (STevor and RIfin iDEntifier) is an HMM-based, command-line program that automates the identification and classification of RIFIN and STEVOR protein sequences in the malaria parasite Plasmodium falciparum. STRIDE is more sensitive in detecting RIFINs and STEVORs than available PFAM and TIGRFAM tools and reports RIFIN subtypes and the number of sequences with a FHEYDER amino acid motif, which has been associated with severe malaria pathogenesis. Conclusions STRIDE will be beneficial to malaria research groups analyzing genome sequences and transcripts of clinical field isolates, providing insight into parasite biology and virulence.

Changes in noradrenaline and dopamine levels under oxygen debt conditions in the brain of rats during experimental acute pancreatitis

This study’s aim was to assess the level of catecholamines, i.e., noradrenaline and dopamine, under oxygen debt conditions in the brain of experimental animals in which acute pancreatitis was experimentally induced. Catecholamines play the role of neurotransmitters and neuromediators. They are responsible for the regulation of motor and emotional processes, take part in the regulation of hormonal activities, sleep, wakefulness, concentration, attention, and learning processes. The experiment also determined the oxygen tension as an indicator of respiratory failure and the activity of amylase and lipase in the development of the inflammatory process. The animals on which the experiment was conducted were Wistar rats (140 animals) divided into 3 research groups: control (C) animals (n = 30), healthy (H) animals (n = 30), and operated (O) animals (n = 80). The determination of amylase, lipase, oxygen pressure, NA, and DO levels were performed at hours 2, 6, 12, 24, and 48 of the experiment. The animals in group C had an injection needle inserted to investigate only the effects of mechanical damage to the organs. On the other hand, the animals in group O had a 5% solution of sodium taurocholate introduced into the common bile-pancreatic duct. The research conducted shows that the most significant changes in NA and DO levels were observed on the first day of the experiment. The concentrations of the above catecholamines were statistically significantly correlated with the level of amylase in the blood. The peak of dopamine was observed between the 6th and 12th hours of the experiment, while the lowest concentration of noradrenaline was observed at the 6th hour of the experiment.